Cancer Treatment Today » Rectal Cancer

Sprycel for colon cancer – pro

M Levin, MD — Fri, 02 Nov 2012 12:54:21 +0000

Dasatinib, also known as Sprycel, is a cancer drug produced by Bristol-Myers Squibb and sold under the trade name Sprycel. It is a drug that is approved by the FDA for chronic myelogenous leukemia. It has an effect on the Src kinases, which interact with the EGFR receptor. One phase II trial(Nautiyal et al) showed that Dasatinib is inactive in previously treated metastatic colorectal patients patients. There is a trial that is studying this drug: Dasatinib in Treating Patients With Previously Treated Metastatic Colorectal Cancer, NCT00504153. This study is ongoing, but not recruiting participants.

An interesting report suggested that curcumin, a turmeric derivative, can increase the effectiveness of Sprycel in colon cancer but this needs to be proven in large, prospective trials.

G. Somlo, F. Atzori, L. Strauss, A. Rybicki, X. Wu, W. Gradishar, J. Specht;Dasatinib plus capecitabine (Cap) for progressive advanced breast cancer (ABC): Phase I study CA180004.J Clin Oncol 27:15s, 2009 (suppl; abstr 1012)

Lisa Hutchinson Targeted therapies: Dasatinib sensitizes KRAS-mutant colorectal cancer tumors to cetuximab Nature Reviews Clinical Oncology 8, 193 (April 2011)

Nautiyal J, Banerjee S, Kanwar SS, Yu Y, Patel BB, Sarkar FH, Majumdar AP. Curcumin enhances dasatinib-induced inhibition of growth and transformation of colon cancer cells.Int J Cancer. 2011 Feb 15;128(4):951-61.

For Lay version see here

IMRT for rectal cancer – pro

M Levin, MD — Thu, 13 Sep 2012 15:29:44 +0000

IMRT is a rapidly evolving technique, which affords a more precise radiation dose delivery of escalated doses, in appropriate cases, to targeted tumors, while sparing nearby healthy tissue structures. The FDA clearance of numerous devices for the technical delivery of IMRT is based on the capability of this technology to incorporate accurate dose calculation algorithms, associated with a verifiable dose distribution, as managed by the treating physician, (i.e., radiation oncologist). Although, to date, no randomized trials have matured to document long-term outcomes data and efficacy for IMRT, the scientific evidence currently available indicates that IMRT permits better treatment planning and sparing of surrounding tissues, which is of particular usefulness with “Radiosensitive” tumors of the head/neck, prostate and CNS lesions where the target volume is in close proximity to critical healthy structures that must be protected. These results may be extrapolated to the treatment of other cancers at other anatomic sites; however, a number of technical issues need to be resolved before IMRT can be recommended routinely. The NCI was sufficiently concerned aboyt these issues to issue a recently updated report for use in planning and design of clicnial trials. It can be found at http://atc.wustl.edu/home/NCI/NCI_IMRT_Guidelines_2006.pdf

A recent retrospective review of 53 uses of IMRT in anal cancer concluded: “Preliminary outcomes suggest that concurrent chemotherapy and IMRT for anal canal cancers is effective and tolerated favorably compared with historical standards.” More studies are needed.

For rectal cancer, the literature suggests that the dose is better distributed and may be better tolerated. What has not yet been proven, however, is the clinical significance of this factor. Thus far, there are no guidelines that recommend IMRT for rectal cancer.

http://atc.wustl.edu/home/NCI/NCI_IMRT_Guidelines_2006.pdf

J. K. Salama, L. K. Mell, D. A. Schomas, R. C. Miller, K. Devisetty, A. B. Jani, A. J. Mundt, J. C. Roeske, S. L. Liauw, and S. J. Chmura
Concurrent Chemotherapy and Intensity-Modulated Radiation Therapy for Anal Canal Cancer Patients: A Multicenter Experience
J. Clin. Oncol., October 10, 2007; 25(29): 4581 – 4586.

National Cancer Institute (NCI). National Cancer Institute Guidelines for the use of Intensity Modulated Radiation Therapy in Clinical Trials. Bethesda, MD: NCI; January 14, 2005

M. Callister, G. Ezzell, L. Gunderson 2143IMRT Reduces the Dose to Small Bowel and Other Pelvic Organs in the Preoperative Treatment of Rectal Cancer
International Journal of Radiation OncologyBiologyPhysics, Volume 66, Issue 3, Pages S290-S290

M.C.W.M. Bloemers, L. Portelance, R. Ruo, M. Duclos, B. Bahoric, L. Souhami A Dosimetric Analysis of IMRT versus 3D Conventional Radiation in Vulvar Cancer
International Journal of Radiation Oncology*Biology*Physics, Volume 72, Issue 1, Supplement 1, 1 September 2008, Pages S362-S363
M. Teresa Guerrero Urbano, Anthony J. Henrys, Elisabeth J. Adams, Andrew R. Norman, James L. Bedford, Kevin J. Harrington, Christopher M. Nutting, David P. Dearnaley, Diana M. Tait Intensity-modulated radiotherapy in patients with locally advanced rectal cancer reduces volume of bowel treated to high dose levels
International Journal of Radiation Oncology*Biology*Physics, Volume 65, Issue 3, 1 July 2006, Pages 907-916

PET to stage rectal cancer – pro

M Levin, MD — Mon, 10 Sep 2012 20:52:08 +0000

There a number of imaging modalities that can stage colon and rectal cancer. A recent study evaluated the impact of FDG-PET on the management of patients with colorectal carcinoma. They noted a change in the clinical stage and major management decisions in approximately 40% of patients. The disease was upstaged in 20 patients (80%) and downstaged in 5 patients (20%). As a result of FDG-PET findings, physicians avoided major surgery in 41% of patients for whom surgery was the intended treatment. On the other hand, false-positive results may occur with FDG-PET in patients with abscesses from nonspecific inflammatory reactions following radiotherapy or tracer uptake in the bowel, bladder, or ureters. Role of PET/CT is less well defined and no guidelines support it for rectal cancer.

NCCN states that PET scan is not routinely indicated. It is not known whether it adds any useful information to that provided by CT.

Wells IT et al,PET/CT in anal cancer – is it worth doing?Clin Radiol. 2012 Jun;67(6):535-40

Agrawal A, Nair N, Agrawal R, Baghel NS. Unsuspected second malignancy detection by FDG PET scan. Clin Nucl Med. Dec 2008;33(12):868-9.

Capirci C, Rubello D, Chierichetti F. Long-term prognostic value of 18F-FDG PET in patients with locally advanced rectal cancer previously treated with neoadjuvant radiochemotherapy. AJR Am J Roentgenol. Aug 2006;187(2):W202-8.

Meta J, Seltzer M, Schiepers C. Impact of (18)f-fdg pet on managing patients with colorectal cancer: the referring physician”s perspective. J Nucl Med. Apr 2001;42(4):586-90.

nccn.org, rectal cancer, 2018

Alimta for colon cancer – pro

M Levin, MD — Wed, 05 Sep 2012 18:17:31 +0000

Pemetrexed (Alimta) shows single-agent activity in advanced colorectal cancer. In two phase II studies in which patients received pemetrexed at 600 mg/m2 or 500 mg/m2 as first-line treatment for metastatic disease, objective response rates were 15.4% and 17.2%. In a National Surgical Adjuvant Breast and Bowel Project phase II trial in 54 patients with previously untreated advanced colorectal cancer, pemetrexed at 500 mg/m2 plus oxaliplatin (Eloxatin) at 120 mg/m2 every 21 days with folic acid/vitamin B12 supplementation resulted in an objective response of 23%.

It has also been combined with irinotecan and randmozed in first-line against Fofiri but did not do as well. Neither efficacy nor safety improved on the ALIRI arm compared to the FOLFIRI arm. Progression-free survival on FOLFIRI was significantly longer compared to ALIRI.

The issue is 2nd line therapy. As a single agent in second line, a study has been competed and results are awaited: A Trial of ALIMTA (Pemetrexed) Plus Irinotecan in Patients Who Have Been Previously Treated For Metastatic Colorectal Cancer, NCT00034502. This is a non-randomized study in patients who have received prior 5-FU therapy for colorectal cancer. The objective of this trial is to establish a maximum tolerated dose of ALIMTA and irinotecan given in combination as well as to assess the safety and efficacy of this combination for patients with locally advanced or metastatic colorectal cancer. ALIMTA and irinotecan will be given every 21 days.

F. Meriggi, B. Di Biasi, C. Caliolo, A. Zaniboni, The Potential Role of Pemetrexed in Gastrointestinal Cancer, Chemotherapy Vol. 54, No. 1, 2008

CHRISTOPHE LOUVET, Premetrexed in Advanced Colorectal Cancer ONCOLOGY. Vol. 18 No. 13 8
2004

Craig Underhill et al, A Randomized Phase II Trial of Pemetrexed plus Irinotecan (ALIRI) versus Leucovorin-Modulated 5-FU plus Irinotecan (FOLFIRI) in First-Line Treatment of Locally Advanced or Metastatic Colorectal Cancer Oncology Vol. 73, No. 1-2, 2007

Xeloda or Xeloda and Oxaliplatin with radiation for rectal cancer – pro

M Levin, MD — Wed, 05 Sep 2012 12:45:03 +0000

Chemoradiation is the preferred approach to upfront treatment of rectal cancer whenever possible.

“Chemoradiation” refers to the carefully orchestrated simultaneous administration of chemotherapy and radiation treatments. Chemoradiation is an important tool in the treatment of rectal cancer. The term “neoadjuvant” refers to the concept of administering chemotherapy and/or radiation therapy prior to surgery. The purpose of neoadjuvant chemoradiation therapy is twofold: to shrink a tumor to facilitate subsequent surgical removal and to improve a patient’s chance for cure. Alternatively, patients with rectal cancer of a size and location that permit resection first should subsequently have adjuvant chemoradiation therapy to improve their chance for a cure.

A typical chemoradiation regimen might consist of daily (Monday through Friday) radiation treatments concurrent with daily (Monday through Friday) continuous infusion 5-fluorouracil (5-FU). This chemoradiation is typically given over a period of five to six weeks. Chemotherapy is given with radiation therapy in order to sensitize tumor cells to radiation, and because the combination has been shown to be more effective than the use of either modality alone. Continuous infusion rather than bolus (a daily 5-10 minute infusion) chemotherapy is preferred as it has resulted in improved survival rates in one study. This regimen may be given pre- or postoperatively for locally advanced tumors (T3/T4 or N1/N2) where it has been shown to reduce the chance of tumor recurrence and improve the chance for cure.
With Xeloda alone, there are two supportive adjuvant phase II studies. Xeloda simulates continuous infusion 5FU and can substitute for it however, the combination of Xeloda and Oxaliplatin is still being investigated with radiation. A phase I/II study from the UK has determined the MTD of continuous (7 days) oral capecitabine administered twice daily in combination with oxaliplatin 130 mg/m2 on days 1 and 29, and pelvic radiotherapy in patients with borderline or unresectable rectal cancer. Now that this study is complete, the regimen is likely to be evaluated in a larger randomised phase III trial.

A German Group performed a phase I study to determine the MTD of oxaliplatin when administered with capecitabine and standard radiotherapy, and extended to a phase II neoadjuvant study in 32 patients with LARC or low-lying rectal cancer. A Belgian trial has used capecitabine 5 days per week given on weekdays only (i.e. capecitabine 825 mg/m2 twice daily on weekdays plus weekly low-dose oxaliplatin 50 mg/m2 on days 1, 8, 15, 22 and 29 plus radiotherapy 45 Gy in 1.8 Gy daily fractions for 5 weeks. This same regimen has also been evaluated in the larger international phase II CORE (capecitabine, oxaliplatin, radiotherapy and excision) study.
Another small dose-finding study is evaluating a similar chemoradiation regimen (capecitabine 725–900 mg/m2 twice daily on weekdays plus escalating doses of oxaliplatin 50 mg/m2, 60 mg/m2, 70 mg/m2 on days 1, 8, 15, 22 and 29 plus radiotherapy 45 Gy in 1.8 Gy daily fractions for 5 weeks). Finally, an ongoing Italian study is examining preoperative capecitabine and oxaliplatin with high-dose pelvic conformal radiotherapy in Locally Advanced Rectal Cancer.

The current findings from the above studies suggest that preoperative capecitabine and oxaliplatin chemoradiation is effective and generally well tolerated, although more robust toxicity data on weekly schedules of oxaliplatin is required. For this reason, a large, phase III pan-European trial (PETACC-6) comparing capecitabine and oxaliplatin chemoradiation with capecitabine chemoradiation alone as adjuvant treatment in T3/4 N1/2 patients is in development. It is recommended by NCCN(REC-4).

Sauer R, Becker H, Hohenberger W, et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 2004;351:1731-1740

G. A. Hospers, C. J. A. Punt, M. E. Tesselaar, A. Cats, K. Havenga, J. W. H. Leer, C. A. Marijnen, E. P. Jansen, H. H. J. M. Van Krieken, T. Wiggers, et al.
Preoperative Chemoradiotherapy with Capecitabine and Oxaliplatin in Locally Advanced Rectal Cancer. A Phase I II Multicenter Study of the Dutch Colorectal Cancer Group
Ann. Surg. Oncol., October 1, 2007; 14(10): 2773 – 2779.

C. Aschele and S. Lonardi
Multidisciplinary treatment of rectal cancer: medical oncology.
Ann. Onc., November 1, 2007; 18(11): 1908 – 1915.

R. Glynne-Jones and M. Harrison
Locally Advanced Rectal Cancer: What Is the Evidence for Induction Chemoradiation?
Oncologist, November 1, 2007; 12(11): 1309 – 1318.

Folfox and Folfiri for metastatic colorectal cancer – pro

M Levin, MD — Wed, 05 Sep 2012 12:20:21 +0000

Currently, there are seven active and approved chemotherapy drugs for patients with metastatic colorectal cancer: 5-FU, capecitabine, irinotecan, oxaliplatin, bevacizumab, cetuximab, and panitumumab. Among the best studied ways of putting some of these drugs together are the regimen Folfox and Folfiri. Three randomized studies demonstrated improved response rates, progression-free survival (PFS), and OS when irinotecan or oxaliplatin was combined with 5-FU-leucovorin. Intergroup study N9741 then compared IFL with FOLFOX4 in first-line treatment for patients with metastatic colorectal cancer. Patients assigned to FOLFOX4 experienced an improved PFS (median, 6.9 months vs. 8.7 months; P = .014; HR = 0.74; 95% CI, 0.61–0.89) and OS (15.0 months vs. 19.5 months, P = .001; HR = 0.66; 95% CI, 0.54–0.82) compared with patients randomized to IFL. Subsequently, two studies compared FOLFOX with FOLFIRI, and patients were allowed to cross over upon progression on first-line therapy, respectively. PFS and OS were identical between the treatment arms in both studies. Since the publication of these studies, the use of either FOLFOX or FOLFIRI is considered acceptable for first-line treatment of patients with metastatic colorectal cancer.Avastin is also approved with 5FU containing regimens for first line. Forfiri is FDA approved also with Erbitux.

The Folfox regimen includes a 22 hour continuous infusion of 5FU. While this can be done through a pump on the outpatient basis, it is often delivered inpatient. The FLOX regimen eliminates the infusion part and is slowly gaining on the Folfox because it is more convenient. However, at the present time, Folfox has more supporting studies and is more widely used than FLOX. Flox is quoted in NCCN, COL-F, 2 2017.
Tournigand, C, Andre, T, Achille, E, et al. FOLFIRI Followed by FOLFOX6 or the Reverse Sequence in Advanced Colorectal Cancer: A Randomized GERCOR Study. J Clin Oncol 2004; 22:229.

Colucci G, Gebbia V, Paoletti G, et al.: Phase III randomized trial of FOLFIRI versus FOLFOX4 in the treatment of advanced colorectal cancer: a multicenter study of the Gruppo Oncologico Dell’Italia Meridionale. J Clin Oncol 23 (22): 4866-75, 2005.
Hurwitz H, Fehrenbacher L, Novotny W, et al.: Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350 (23): 2335-42, 2004.
Giantonio BJ, Catalano PJ, Meropol NJ, et al.: High-dose bevacizumab improves survival when combined with FOLFOX4 in previously treated advanced colorectal cancer: results from the Eastern Cooperative Oncology Group (ECOG) study E3200. J Clin Oncol 23 (Suppl 16): A-2, 1s, 2005.
Rothenberg ML, Eckardt JR, Kuhn JG, et al.: Phase II trial of irinotecan in patients with progressive or rapidly recurrent colorectal cancer. J Clin Oncol 14 (4): 1128-35, 1996.
nccn.org, colorectal 2014

Van Cutsem E, Köhne CH, Láng I, et al. Cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumor KRAS and BRAF mutation status. J Clin Oncol. 2011;29(15):2011-2019.

Daniela R. Nebuloni Milena P. Mak Fabiano Hahn Souza Daniel F. Saragiotto Thiago Júlio Gilberto De Castro Jr Jorge Sabbaga Paulo M. Hoff, Modified FLOX as first-line chemotherapy for metastatic colorectal cancer patients in the public health system in Brazil: Effectiveness and cost-utility analysis Mol CLin Oncol January 2013 Volume 1 Issue 1

Kuebler JP, Wieand HS, O’Connell MJ, et al. Oxaliplatin combined with weekly bolus fluorouracil and leucovorin as surgical adjuvant chemotherapy for stage II and III colon cancer: results from NSABP C-07. J Clin Oncol. 2007:25:21982204.

Neoadjuvant chemoradiation in rectal cancer – pro

admin — Sun, 02 Sep 2012 14:26:04 +0000

Lay Summary: Chemoradiation is the preferred approach to upfront treatment of rectal cancer whenever possible.

“Chemoradiation” is combined simultaneous administration of chemotherapy and radiation treatments. Chemoradiation is an important tool in the treatment of rectal cancer. The term “neoadjuvant” refers to the concept of administering chemotherapy and/or radiation therapy prior to surgery. The purpose of neoadjuvant chemoradiation therapy is twofold: to shrink a tumor to facilitate subsequent surgical removal and to improve a patient’s chance for cure. It follows that even thel cancer of a size and location that permit resection first should subsequently have adjuvant chemoradiation therapy to improve their chance for a cure.

Sauer R, Becker H, Hohenberger W, et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 2004;351:1731-1740

O’Dwyer, P. J., Eckhardt, S. G., Haller, D. G., Tepper, J., Ahnen, D., Hamilton, S., Benson, A. B. III, Rothenberg, M., Petrelli, N., Lenz, H.-J., Diasio, R., DuBois, R., Sargent, D., Sloan, J., Johnson, C. D., Comis, R. L., O’Connell, M. J. (2007). Priorities in Colorectal Cancer Research: Recommendations From the Gastrointestinal Scientific Leadership Council of the Coalition of Cancer Cooperative Groups. JCO 25: 2313-2321

nccn.org, colorectal 2018

Preoperative chemotherapy and radiation for rectal cancer – pro

admin — Sun, 02 Sep 2012 00:16:58 +0000

Lay Summary: About NSABP-04

NSABP R-04 is “A Clinical Trial Comparing Preoperative Radiation Therapy and Capecitabine with or without Oxaliplatin with Preoperative Radiation Therapy and Continuous Intravenous Infusion of 5-Fluorouracil with or without Oxaliplatin in the Treatment of Patients with Operable Carcinoma of the Rectum. The primary objective is to compare the rate of local-regional relapse in patients with resectable rectal cancer treated with chemoradiotherapy comprising radiation therapy and either capecitabine or fluorouracil with or without oxaliplatin; there are 9 secondary objectives.

The investigators of the NSABP R-04 trial have been working diligently for years to launch their important study evaluating the role of oral fluoropyrimidine-based neoadjuvant chemoradiotherapy. The lengthy clinical trial development process outlined above has exposed the NSABP R-04 trial to external factors beyond the investigators’ control (in particular, to corporate and US Food and Drug Administration decisions) that have caused its design to be changed and delayed its activation. Now, the emergence of new data in the adjuvant treatment of colorectal cancer (the Xeloda in Adjuvant Colon Cancer Therapy [X-ACT] trial2 and the MOSAIC trial3) has diminished the novelty of the original question posed by the NSABP R-04 trial but strengthened the concept of neoadjuvant chemoradiotherapy (the German Rectal Cancer Study). The trend toward improved disease-free survival for capecitabine in the X-ACT trial, suggests strongly that capecitabine is an appropriate treatment to examine in R-04, and the demonstration of improved disease-free survival in adjuvant colon cancer for an oxaliplatin containing regimen in the MOSAIC trial mandates the consideration of an oxaliplatin regimen in rectal cancer.

In summary, this is a trial that poses a number of important questions. Until they are resolved, properative chemo-radiation with xeloda and oxapliplatin containing regimens remain experimental, even though they are already being used in the clinic.

Adjuvant therapy of rectal cancer, including stage II – pro

M Levin, MD — Mon, 27 Aug 2012 18:17:52 +0000

Adjuvant chemotherapy for Stage II colon cancer is controversial but the field is now returning back to it and guideliens state that it is optional but accepted. There is greater acceptance for rectal cancer and NCCN lists Folfox or capecitabine with oxaliplatin. for adjuvant therapy of rectal cancer for stage II or III. Following neoadjuvant chemo, resection, adjuvant treatment recommendations per REC-4 lists FOLFOX and CapeOx.

Another point of uncertainty In rectal cancer is regarding preoperative versus postoperative treatment, ot both, and guidelines provide guidance in either situation. The one randomized study in the USA, R-03, that looked at the question found both approaches to be comparable. A German study is ongoing, with 800 patients. Both regimens incorporate four cycles of 5-day 5-FU administered in the postoperative setting.

Stage T3N0M0 is a special case, becasue much of the older literature may ahve understaged these patients. Now that endorectal uoltasound is routinely performed, there is more confedence that N0 really means “no invovled nodesP. NCCN at this point recommends chem for this group as well.

Roh MS, Petrelli N, Wieand S, et al: Phase III randomized trial of preoperative versus postoperative multimodality therapy in patients with carcinoma of the rectum (NSABP R-03) (abstract 490). Proc Am Soc Clin Oncol 20:123a, 2001.

NCCN.ORG, Colon Cancer 2013, REC-4

Capecitabine and Oxaliplatin in the Adjuvant Treatment of Stage III (Dukes’ C) Colon Cancer (TA100)
Technology Appraisal Guidance No. 100

http://www.mims.co.uk/Guidelines/882146/Capecitabine-Oxaliplatin-Adjuvant-Treatment-Stage-III-Dukes-C-Colon-Cancer-TA100/ 2009

Lisa A. Kachnic et al, Rectal Cancer at the Crossroads: The Dilemma of Clinically Staged T3, N0, M0 Disease, ournal of Clinical Oncology, Vol 26, No 3 (January 20), 2008: pp 350-351

Xeloda or 5FU, leukovorin and gemcitabine for colorectal cancer – pro

M Levin, MD — Mon, 27 Aug 2012 18:07:25 +0000

Fluoropyrimidines with oxaliplatin or irinotecan plus bevacizumab is the standard chemotherapy combination in patients with advanced colorectal cancer (CRC). Gemcitabine acts synergistically with fluoropyrimidines to enhance the binding of thymidylate synthase and increase inhibition of DNA synthesis.
The patient appealed based on studies of Xeloda/Gemcitabine and assumes the identity of 5FU/leukovorin to Xeloda, which is far from proven in rectal cancer. Even if assuming such equivalence, it remains an experimental combination; A 2004 study concluded: “This combination regimen has an excellent tolerance in this heavily pretreated patients; the MTP, survival (OS) and the founding of some degree of activity are encouraging. Further studies of this treatment regimen are warranted.”
The regimen has more of a track record in pancreatic cancer and renal cell cancer.
A recent review looked at forty-two advanced CRC patients who were evaluated in two Phase I studies and the maximum tolerated dose of gemcitabine was 900 – 1,000 mg/m(2) weekly with either bolus 5-fluorouracil (5-FU) or capecitabine. A total of 216 advanced CRC patients were evaluated in six Phase II studies. It found that “Fluoropyrimidine plus gemcitabine is clinically active in patients with refractory CRC demonstrating prolonged median time to progression and acceptable toxicity only when bolus 5-FU was not used.”
Clinicaltrials.gov lists one study that has been completed but for which no publication has yet been submitted.

Y. Fernández, J. M. Vieitez, J. Fra, I. Palacio, B. Mareque, E. Uña, J. M. Buesa, A. J. Lacave; Hospital Central de Asturias, Oviedo, Spain Capecitabine plus gemcitabine in heavily pre-treated colorectal cancer. Results of an exploratory study.Journal of Clinical Oncology, 2004 ASCO Annual Meeting Proceedings (Post-Meeting Edition). Vol 22, No 14S (July 15 Supplement), 2004: 3679

Merl M, Hoimes C, Pham T, Saif MW.
Is there a palliative benefit of gemcitabine plus fluoropyrimidines in patients with refractory colorectal cancer? A review of the literature previously presented: poster at the 2008 Gastrointestinal Cancer Symposium (Abstract No. 512).Expert Opin Investig Drugs. 2009 Sep;18(9):1257-64.